Home > Publications Database > 5-methylcytosine and 5-hydroxymethylcytosine in brains of patients with multiple system atrophy and patients with Parkinson's disease. > print

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024 7 _ |a 10.1016/j.jchemneu.2018.12.005
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024 7 _ |a pmid:30557654
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024 7 _ |a 0891-0618
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024 7 _ |a 1873-6300
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037 _ _ |a DZNE-2020-06873
041 _ _ |a English
082 _ _ |a 610
100 1 _ |a Kaut, Oliver
|0 P:(DE-HGF)0
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|e Corresponding author
245 _ _ |a 5-methylcytosine and 5-hydroxymethylcytosine in brains of patients with multiple system atrophy and patients with Parkinson's disease.
260 _ _ |a Amsterdam [u.a.]
|c 2019
|b Elsevier Science
264 _ 1 |3 print
|2 Crossref
|b Elsevier BV
|c 2019-03-01
336 7 _ |a article
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336 7 _ |a ARTICLE
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336 7 _ |a JOURNAL_ARTICLE
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336 7 _ |a Journal Article
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520 _ _ |a Multiple system atrophy (MSA) is a sporadic neurodegenerative disorder of unknown etiology, characterized pathologically by α-synuclein aggregates preferentially found in oligodendroglial cells. DNA methylation has emerged as a mechanism of regulation of α-synuclein expression. Reduced 5-methylcytosine (5-mC) DNA methylation of α-synuclein has been found in the brains of patients with Parkinson's disease (PD). 5-hydroxymethylcytosine (5-hmC) methylation is another epigenetic modification of DNA. It is involved in the de-methylation of DNA, gene regulation, and DNA repair mechanisms. Here, we examined sections of human paraffin-embedded brain tissue from the cerebellum and brain stem, including the substantia nigra pars compacta, of patients with PD (n = 8) and MSA (n = 8) as well as age-matched controls (n = 8). The neocortical tissue of PD patients (n = 10) and controls (n = 10) was also examined. Using immunohistochemistry, we analyzed the expression of 5-mC and 5-hmC with an automatic, rater-independent semi-quantification method. We found a significant upregulation of 5-mC, but not 5-hmC, in cortical sections from PD patients. The brain stem and substantia nigra, and in particular the dopaminergic neurons, showed unchanged levels of both 5-mC- and 5-hmC-immunoreactivity in all groups. In the cerebellum, 5-mC was significantly decreased only in MSA patients in the granule cell layer; in contrast, 5-hmC was significantly upregulated in the cerebellar white matter of both PD and MSA patients. Our study showed different levels of expression of total 5-mC and 5-hmC methylation across different brain regions in PD and for the first time in MSA. Our results indicate that 5-mC may be relevant in MSA. The underlying mechanism of the differential 5-mC and 5-hmC expression remains unclear.
536 _ _ |a 344 - Clinical and Health Care Research (POF3-344)
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542 _ _ |i 2019-03-01
|2 Crossref
|u https://www.elsevier.com/tdm/userlicense/1.0/
588 _ _ |a Dataset connected to CrossRef, PubMed,
650 _ 2 |a 5-Methylcytosine: analogs & derivatives
|2 MeSH
650 _ 2 |a 5-Methylcytosine: analysis
|2 MeSH
650 _ 2 |a 5-Methylcytosine: metabolism
|2 MeSH
650 _ 2 |a Aged
|2 MeSH
650 _ 2 |a Aged, 80 and over
|2 MeSH
650 _ 2 |a Brain: metabolism
|2 MeSH
650 _ 2 |a Female
|2 MeSH
650 _ 2 |a Humans
|2 MeSH
650 _ 2 |a Male
|2 MeSH
650 _ 2 |a Middle Aged
|2 MeSH
650 _ 2 |a Multiple System Atrophy: metabolism
|2 MeSH
650 _ 2 |a Parkinson Disease: metabolism
|2 MeSH
693 _ _ |0 EXP:(DE-2719)IDAF-20190308
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700 1 _ |a Kuchelmeister, Klaus
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700 1 _ |a Möhl, Christoph
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700 1 _ |a Wüllner, Ullrich
|0 P:(DE-2719)2000056
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773 1 8 |a 10.1016/j.jchemneu.2018.12.005
|b : Elsevier BV, 2019-03-01
|p 41-48
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|t Journal of Chemical Neuroanatomy
|v 96
|y 2019
|x 0891-0618
773 _ _ |a 10.1016/j.jchemneu.2018.12.005
|g Vol. 96, p. 41 - 48
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|p 41-48
|t Journal of chemical neuroanatomy
|v 96
|y 2019
|x 0891-0618
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910 1 _ |a Deutsches Zentrum für Neurodegenerative Erkrankungen
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910 1 _ |a Deutsches Zentrum für Neurodegenerative Erkrankungen
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